Barone Rita, Fiumara Agata, Jaeken Jaak
Department of Pediatrics, Pediatric Neurology, University of Catania, Catania, Italy.
Department of Pediatrics, Center for Metabolic Disease, KULeuven, Leuven, Belgium.
Semin Neurol. 2014 Jul;34(3):357-66. doi: 10.1055/s-0034-1387197. Epub 2014 Sep 5.
Congenital disorders of glycosylation (CDG) are genetic diseases due to defective glycosylation of proteins and lipids. The authors present an update on these disorders affecting the central nervous system with a focus on cerebellar involvement. The rate of identification of novel CDG shows an exponential increase. Some 76 CDG are actually known, not taking into account the defects in glycan-modifying proteins. Neurologic involvement is present in the large majority of CDG. Screening methods are limited to serum transferrin isoelectrofocusing (for N-glycosylation disorders with sialic acid deficiency), and serum apolipoprotein C-III isoelectrofocusing (for core 1 mucin-type O-glycosylation disorders). Whole exome/genome sequencing is increasingly used in the diagnostic workup of patients with CDG-X. Treatment is greatly lagging behind because only one CDG is efficiently treatable (MPI-CDG). Cerebellar involvement is an important feature of PMM2-CDG, the congenital muscular dystrophies due to dystroglycanopathy, and SRD5A3-CDG. It has also been reported in some patients with ALG1-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, ALG8-CDG, PIGA-CDG, DPM1-CDG, DPM2-CDG, B4GALT1-CDG, SLC35A2-CDG, COG1-CDG, COG5-CDG, COG7-CDG, and COG8-CDG.
先天性糖基化障碍（CDG）是由于蛋白质和脂质糖基化缺陷引起的遗传性疾病。作者介绍了这些影响中枢神经系统的疾病的最新情况，重点是小脑受累情况。新型CDG的识别率呈指数级增长。实际上已知约76种CDG，未考虑聚糖修饰蛋白中的缺陷。绝大多数CDG都有神经系统受累情况。筛查方法仅限于血清转铁蛋白等电聚焦（用于诊断缺乏唾液酸的N-糖基化障碍）和血清载脂蛋白C-III等电聚焦（用于诊断核心1粘蛋白型O-糖基化障碍）。全外显子组/基因组测序在CDG-X患者的诊断检查中越来越常用。治疗方面严重滞后，因为只有一种CDG可有效治疗（MPI-CDG）。小脑受累是PMM2-CDG、由肌营养不良聚糖病引起的先天性肌营养不良以及SRD5A3-CDG的重要特征。在一些ALG1-CDG、ALG3-CDG、ALG9-CDG、ALG6-CDG、ALG8-CDG、PIGA-CDG、DPM1-CDG、DPM2-CDG、B4GALT1-CDG、SLC35A2-CDG、COG1-CDG、COG5-CDG、COG7-CDG和COG8-CDG患者中也有相关报道。
